Keywords

8.1 Introduction

The COVID-19 pandemic has been a public health emergency (PHE) on a global scale, impacting all nations and peoples. As is already known from previous health emergencies, even when the pathological agent is nonselective, different people and countries are affected differently. Frequently these differences are not due to individual characteristics but to precarious contexts that became even less safe than before (Khetan et al. 2022). An unknown disease that affects the world in a rapid manner brings many challenges. These range from an initial lack of knowledge about the biological effects of the viral infection and how to treat it, to its impacts on resources and economies. Inequitable COVID-19 vaccine distribution can be understood as a categorical example of how the pandemic has had different impacts on different countries and populations, and has exacerbated vulnerabilities (Acharya et al. 2021; VOA News 2021; Basak et al. 2022; Fisseha et al. 2021).

The importance of a comprehensive and considered account of vulnerability in research ethics has been discussed for decades (Luna 2009, 2019; Hurst 2008; Lange et al. 2013). In order to provide an overview of the concept of vulnerability, we will examine at least three dimensions of vulnerability discussed in the literature: the individual, the structural and the relational. We will also show how these dimensions can overlap and intersect in dynamic and relational ways, especially during PHEs, such as the COVID-19 pandemic (Luna 2009, 2019; The Lancet 2020). The cases presented in this chapter provide examples of how the COVID-19 pandemic exacerbates pre-existing vulnerabilities and show why it is important to reflect on this. Clearly, there is an ethical imperative for research data to reflect the needs of the most vulnerable populations.

Economic and political instability, along with insufficient medical and social protection resources, have been important drivers of the worsening inequities and inequalities seen during the COVID-19 pandemic (Rocha et al. 2021; Etienne 2022; Busso and Messina 2020). The widening of social, racial, gender and economic inequalities worsens existing vulnerabilities and creates new ones. In this context, ethical issues must be carefully considered when research is carried out with populations who face historical and socio-economic structural inequalities. These considerations also affect how we should think about research ethics during PHEs with populations in disadvantaged contexts. The exclusion of groups or individuals as research participants is an approach that in many instances leads to the worsening of vulnerabilities, and inclusion strategies should always be adopted.

8.2 Conceptualizations of Vulnerability

On the individual level, the idea of vulnerability is related to the postulation that every individual has fragilities requiring safeguards (Butler 2010, 2016). Precariousness is understood as a condition shared by all living beings, owing to our dependence on contexts and our interdependence with each other, which has been defined as the “inherent source of vulnerability” (Lange et al. 2013; Butler 2010). As such, precariousness, or our inherent vulnerability, can be seen as an equalizing generalized condition of human beings. Yet, in certain situations where populations face structural determinants of inequality, this omnipresent condition of fragility is experienced differently.

Case 8.1 prompts reflection on the exclusion of pregnant women from clinical trials for the COVID-19 vaccine. The discussion of vulnerability proves essential when thinking about research ethics in this situation for at least two reasons. Against a background of gender inequity and the historical relativization of women’s autonomy during pregnancy, important questions arise about when pregnant women are not offered the opportunity to make an informed decision about participation in vaccine trials for an emerging disease. At the start of the COVID-19 pandemic pregnant women were deemed too vulnerable to participate in vaccine trials, though not vulnerable enough to the effects of the virus to receive the vaccine during initial vaccine rollouts.

Pregnant women should not be considered vulnerable simply by virtue of being pregnant (CIOMS 2016). The consequences of an initial categorical exclusion from vaccine research were dramatic for pregnant women in the most precarious contexts. COVID-19 was found to be associated with an increased risk of maternal morbidity and mortality (Metz et al. 2022). Many countries in the global South had rates of maternal mortality due to COVID-19 five to ten times higher than those in countries in the global North (PAHO and WHO 2021). Most of the pregnant women hospitalized with COVID-19 were unvaccinated (Engjom et al. 2022). The assumption that a category of people (pregnant women) should be excluded from research trials on the basis of pre-existing vulnerabilities becomes fundamentally flawed when it creates and worsens vulnerabilities. It can be argued that evidence suggests that this exclusion from COVID-19 vaccine trials led, at least in some part, to harm, not protection, for pregnant women and exemplifies how, in research, vulnerabilities should guide our focus, not avert it.

Vulnerability also has structural dimensions; that is, there are economic, social and cultural dynamics that create power differentials (Palk et al. 2020). Contexts of inequality and inequity produce conditions for deprivation and oppression of certain individuals, groups or populations (Butler 2016; Malmqvist 2017). Researchers and bioethicists commonly describe individuals or groups who face structural social and health inequalities as vulnerable, as seen in the Helsinki Declaration (World Medical Association 2013). Initial ideas of vulnerability were mostly categorical – e.g. pregnant individuals (Case 8.1), psychiatric populations (Case 8.2) or extremely poor people (Case 8.3). Although the categorical understanding of vulnerability has been an important step towards trying to solve issues of vulnerability in research, it carries limitations.

Cases 8.1–8.4 in this chapter illustrate how a lack of social protection and public services, impoverishment, social and gender inequalities, disabilities, racism and discrimination compound the many other factors that expose some populations to “layers of vulnerability”. The concept of “layers of vulnerability”, proposed by Florencia Luna (2009), provides a framework that helps us understand how the different dimensions of vulnerability are connected and how they interact with each other: “The metaphor of a layer gives the idea of something ‘softer’, something that may be multiple and different, and that may be removed layer by layer. It is not ‘a solid and unique vulnerability’ that exhausts the category; there might be different vulnerabilities, different layers operating” (Luna 2009, p. 128). Some layers of vulnerability may have a cascading effect, “which may create further layers of vulnerability or worsen existing ones” (Palk et al. 2020, p. 161). The idea of dimensions that intersect, interact, overlap and affect each other can also aid in the understanding of how these layers create contexts that make people vulnerable and points to the limitations of a categorical approach to vulnerability.

When analysing Cases 8.3 and 8.4, it is important to note that poverty and social exclusion have been defined not only as structural issues, but also as relational and fluid processes that are thought to be “driven by unequal power relationships interacting across an economic, political, social and cultural dimension and operating at different levels, including individual, household, group, community, country and global levels” (Ravinetto et al. 2013). These processes are considered to be important conditions that create vulnerabilities in medical research because they lead to health inequalities and diminished autonomy (Popay 2010). Thus, the relational aspect of vulnerabilities speaks to how these conditions interplay and interact in making someone vulnerable in a specific context. Research is inherently a context that impacts these dimensions, and can, therefore, add layers or trigger a cascade of vulnerabilities. The Nuffield Council on Bioethics and the Council for International Organizations of Medical Sciences (CIOMS) also remark on how vulnerabilities are dependent on the context (CIOMS 2016; Nuffield Council on Bioethics 2015, 2020). This indicates the complexity of vulnerability as far as research processes are concerned, even though its consideration is central to ethical practice.

Case 8.2 gives us the opportunity to reflect on research during the COVID-19 pandemic with groups that have specific needs. As this case shows, face-to-face contact can be essential when interacting with institutionalized or hospitalized psychiatric participants. At the same time, researchers need to be aware that some situations might expose participants to a harmful emerging virus. Researchers must be very careful when assessing situations in which limitations on autonomy are already imposed by structures of power, such as in a psychiatric unit or detention centre. These contexts can demonstrate how structural imposition of restrictions on autonomy can trigger a cascade of vulnerability. Adding a pandemic to this situation should draw scrutiny, as participants might feel inclined to participate in research because of a lack of other visitors or because the staff are paying them less attention. Here we can see how a PHE creates an urgent demand for research on the pandemic’s impact on populations who already live in vulnerable contexts. This highlights the importance of considering how best to care for and address the urgent needs of populations living in residential facilities with restrictions on their freedoms, including prisons and other detention facilities.

The cases presented in this chapter aim to provoke reflection not only on concepts of vulnerability, but also on the necessity of thinking creatively and broadly about how to foster conditions that guarantee an inclusive approach in the research setting while promoting protection for research participants and their communities. In the course of a health emergency, the information produced by scientific inquiry becomes essential – especially as a way of dealing with the emergency itself. However, PHE situations are also known to exacerbate the conditions for increased vulnerabilities or to trigger their layers (Nuffield Council on Bioethics 2020; Kass et al. 2019; Chattu and Yaya 2020). Thus, combining an acknowledgement of vulnerability as an inherent possibility of the human condition (the individual dimension) with a context-sensitive analysis (structural and relational dimensions) can provide a way to reach a broader comprehension of all that is at play when thinking about research participation (Rogers et al. 2012). In particular, the provision of an effective approach to protecting participants during emergencies requires careful analysis of and attention to the individual, structural and relational dimensions of vulnerability.

Case 8.4 exemplifies the absence of people with disabilities from research during the pandemic. The WHO has notified some of the ways people with disabilities can be disproportionally impacted during the COVID-19 outbreak (WHO 2020). The exclusion of people with disabilities from research increases their vulnerabilities and leaves significant knowledge gaps regarding their health, needs and rights. In addition, it is important to recognize that COVID-19 can have long-term effects, including chronic health problems and increased susceptibility to disease. These also disproportionately impact those who live with multiple health disparities (Briggs and Vassall 2021). Disability-inclusive approaches to research should not be restricted to responses during a PHE; research practices should be recognized as making a fundamental contribution to understanding impacts and creating adequate and effective responses. These approaches should not only address the challenges and barriers people with disabilities face but also be undertaken in coordination with beneficiaries and existing sectors in civil society, and with health and social programmes (Banks et al. 2021).

8.3 Vulnerability and Inclusion in Research Ethics

Bioethics principles such as autonomy, beneficence and maleficence represent important ethical values; nevertheless, without careful analysis of the complexities of specific contexts which produce vulnerabilities, these values can become abstract and may result in the application of principles in ways that are not appropriately responsive to the context (Nuffield Council on Bioethics 2020). The recognition of different dimensions of vulnerability also means that understanding of this concept may not be assumed to be self-evident. From this perspective, research procedures may be considered ethically sound by research ethics committees, but perceived differently by a community or by grassroots organizations (Nuffield Council on Bioethics 2020).

Although the need to take vulnerability into account in research studies necessitates protection strategies, the idea of vulnerability has also been used to justify the categorical exclusion of individuals or of whole categories of people from research studies. The systematic exclusion of groups historically labelled as vulnerable, such as those living with food insecurity (Case 8.3), pregnant women (Case 8.1), people with disabilities (Case 8.4) or institutionalized people (Case 8.2) has led to a lack of imagination about who needs care, how to support autonomy and how to provide care for these groups (Dashraath et al. 2020; Stemple et al. 2016; Palk et al. 2020). Exclusion reinforces a lack of reflection and experience amongst researchers and research ethics committees (REC) on how to conduct ethical research with these groups (O’Mathúna and Siriwardhana 2017; Spiegel 2017). The consequences of categorical exclusions in the name of participant protection have deepened the marginalization of certain people and groups, as well as precluding them from enjoying the possible benefits of research participation and hindering scientific advancements of relevance to them.

It is important to consider how to promote the participation of people who have been historically excluded from studies, especially as the need for inclusive approaches is increasingly being recognized (Nuffield Council on Bioethics 2020). Guaranteeing conditions for inclusion and participation has been seen as a central aspect of ethical practice in research (Diniz 2019). Pregnant women, as seen in Case 8.1, are an example of a group that has been traditionally excluded from drug and vaccine trials (Beigi et al. 2021; Krubiner et al. 2021). The exclusion of pregnant women from vaccine trials during the COVID-19 pandemic and the Zika epidemic demonstrates the deficiencies of much decision-making undertaken far from people’s realities, similarly to the negative consequences of categorical exclusions evidenced in the HIV crisis (MacQueen and Auerbach 2018; Treatment Action Group 2021; HIV Prevention Trials Network 2009; Schuklenk 2003).

There is growing evidence attesting to the impact that considering the perspectives and opinions of those in the field can have on creating more inclusive research practices (Diniz 2019; MacQueen and Auerbach 2018). Efforts are needed to create conditions for inclusion and for benefit-sharing processes compatible with participants’ and communities’ world views. In settings where individuals are impacted by political, social or economic inequalities, participant protection procedures should also involve an analysis of the pre-existing layers of vulnerability that can be activated or added to by research participation.

Case 8.3 draws attention to how research in settings where even the most basic needs are not being met creates ethical tensions between the participants’ reality and standard research procedures, which require sensitive and contextually appropriate resolution. This is particularly important when planning or conducting research with populations that live with extreme vulnerabilities and when, as a result, the research might be one of the few opportunities for them to gain information or even professional attention. Case 8.3 also demonstrates how the pandemic disproportionally increased vulnerabilities in populations experiencing historical and structural social, racial, gendered and economic disadvantages. In addition to identifying the factors that influence the impacts of the pandemic, it is also important that research focuses on investigating how to build conditions that will help to develop community-centred solutions for preparedness and response in a PHE (Maxmen 2021).

One way of reimagining ethical participant protection procedures is to listen to and understand people’s stories, biographies and needs, as is often undertaken in qualitative studies (Diniz 2019; Palk et al. 2020). These require not only knowledge of the local context by the researchers and RECs, but also imaginative and creative processes. Qualitative research has shown novel intersectional models for the inclusion of research participants, building of trust, and joint individual or community participation in research design and evaluation (Abramowitz et al. 2015; Pratt et al. 2020; Den Hollander et al. 2018). These approaches have strengthened inclusion and accountability for the community and brought recognition and validity to research protocols.

8.4 Vulnerability and the Promotion of Protection and Accountability

Community-based approaches play an important role in the identification of layers of vulnerability during the design of a research protocol or in the course of conducting the study (WHO 2016). A participatory approach requires research practices that acknowledge the imbalances of power and allow for attitudes and processes that address inequalities using combinations of different strategies (Lee et al. 2008; Diniz and Ambrogi 2017). That is, even the allocation of resources by the global North to the global South can be perceived as ethically questionable when the most urgent needs of communities and individuals are not addressed (Schuklenk 2014). As some layers of vulnerability are not readily evident and might not be identifiable to an outsider, there is an unjustifiable risk that research practices may reproduce or worsen inequalities if these vulnerabilities are not accounted for during research processes.

Consequently, protocols incorporating categorical approaches to exclusion criteria often insufficiently account for vulnerability and provide partial protection at best. In fact, these approaches can add vulnerabilities, limit understanding and narrow the reach of research benefits. As researchers, we find that these processes can also stifle our imagination and limit our ability to think about how to conduct research with populations in the most precarious contexts. There is no set number of layers of vulnerability that can justify categorical exclusions. Categorical exclusions do not afford protection. The issue of vulnerability in research should be addressed by creating ways of inclusion and protection that account for the layers of vulnerability.

Recognition of the circumstances of all those involved in a study can inform and expand understandings regarding research practices. That is not to say that the roles of researchers, participants and other individuals who form part of the research ecosystem should become blurred or confusing. Instead, it points to the need to recognize the value of a multidisciplinary, intersectional and representative approach, and to use imagination and creativity when thinking about appropriate research processes. This requires research practices that acknowledge the inherent imbalances of power and allow for attitudes and processes that seek equity and protection through inclusion.

There is no single answer to the question of how issues of vulnerability and inclusion should be addressed in research ethics. The commitment, however, is an ethical one – identifying and creating conditions that support inclusion and the development of protections that account for vulnerabilities, including in research responses to public health emergencies. For this, people in contexts that place them in the most precarious situations must be at the centre of the discussions about research ethics and global health governance. It is important to shift away from systems and structures that reproduce and perpetuate inequalities through fixed exclusionary approaches to vulnerability in order to create new methods for ensuring research accountability. Horizontal and long-lasting relationships with communities can amplify perspectives and decrease distances between researchers and potential participants and their communities. A commitment to decrease vulnerabilities, improve protection and enhance ethical practices entails developing approaches, alongside local groups and communities, to promote inclusion.